In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. Unless otherwise noted, all seminars are held on Wednesdays in the Molecular Science and Engineering Building ("M" Building) in G011 (Cherry Logan Emerson Lecture Theater) at 4:00 p.m. Refreshments are served at 3:30 p.m. in the Emerson-Lewis Reception Salon.

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Engineering Motif-Specific Antibodies: A New Era for Cell Signaling

Highly complex signaling networks control biological processes ranging from development and homeostasis to cell death. Abnormal regulation of signaling networks can result in cancer, neurodegenerative diseases, and diabetes. Consequently, a better understanding of the molecular mechanisms that underlie both normal and abnormal cellular responses will identify new disease-related markers and therapeutic targets. Cells employ a combination of biophysical and biochemical events to elicit a cellular response. In particular, chemical or post-translational modification (PTM) of key proteins provides cells with a highly dynamic way to both transmit and store information. However, accurate detection and quantification of PTMs often requires the generation of PTM-specific antibodies. Traditional antibody generation platforms that rely upon the immunization of animals or in vitro display methods exhibit poor success rates for the development of PTM-specific antibodies.

I will discuss a renewable synthetic antibody strategy to develop PTM-specific antibodies via the engineering of a novel motif-specific binding pocket into an antibody scaffold. Inspired by a natural phosphate-binding motif, I designed and structurally characterized antibody scaffolds with binding pockets specific for three common modifications: phosphoserine, phosphothreonine, and phosphotyrosine. The combination of these novel scaffolds with in vitro antibody generation methods then enabled the rapid generation of fifty phospho- and target-specific antibodies against 70% of the targets. Ultimately, this engineered scaffold strategy may provide a general solution for the rapid, robust development of renewable anti-PTM or anti-peptide antibodies for signaling, diagnostic, and therapeutic applications.